The juvenile form of Batten disease is an autosomal recessive neurodegenerative disease of childhood (Boustany R -M, et al., Am. J. Med. Genet. Suppl. 5: 47–58 (1988)). It is clinically characterized by onset at age 5–6 years with progressive blindness, generalized and myoclonic seizures, cognitive and motor decline and death in the mid to late twenties (Boustany R -M and Kolodny E H Rev. Neurol. (Paris) 145: 105–110 (1989); Boustany R -M Am. J. Med. Genet. 42: 533–535 (1992); Boustany R -M and Filipek P J. Inher. Metab. Dis. 16: 252–255 (1993)).
The CLN3 gene hypothesized to underly juvenile Batten disease encodes a 438 amino acid protein containing six putative hydrophobic transmembrane domains (The International Batten Disease Consortium Cell 82: 949–957 (1995); Janes R W et al., FEBS Lett. 399: 75–77 (1996)). It is expressed in a variety of human tissues including brain. The CLN3 protein is highly conserved across species including dog, mouse, Caenorhabditis elegans and Saccharomyces cerevisiae: (Altshul S F, et al., J. Mol. Biol. 215: 403–410 (1990); Mitchison H M, et al., Genomics 40: 346–350 (1997)).
It has been debated whether the function of the intact CLN3 gene is antiapoptotic, and that its integrity might be necessary for neuronal and photoreceptor survival. (See, e.g., Howard M K, et al., J. Neurochem. 60:1783–1791 (1993); Kulkarni G V and McCulloch C A J. Cell Sci. 107:1169–1179 (1994); Kulkarni G V and McCulloch C A J. Cell Sci. 107: 1169–1179 (1994) Kulkarni G V and McCulloch C A J. Cell Sci. 107: 1169–1179 (1994); Walker P R, et al., Cancer Res. 51: 1078–1085 (1991); Bertand R, et al., Exp. Cell Res. 211: 314–321 (1994); Stoll C, et al., Cancer Res. 36: 2710–2713 (1976)). An antiapoptotic function for intact CLN3 is not generally accepted.